If one accepts the view that behavior is the product of neuronal activity, then it is reasonable to examine the influence of hormones on brain cells in the neural circuits that mediate hormone-regulated behaviors. We propose that hormone-dependent changes in norepinephrine (NE) neurotransmission in the hypothalamus and preoptic area participate in estradiol (E2) and progesterone (P) regulation of female reproductive behavior. Preliminary work from this laboratory demonstrates that administration of physiological relevant doses of E(2) and P in vivo modulates signal transduction by two NE receptor subtypes, beta- and alpha1-adrenoceptors, in the hypothalamus and preoptic area. The goal of the proposed research is to elucidate the molecular mechanism(s) by which E2 and P modulate signal transduction by beta and alpha1-adrenoceptors in the hypothalamus and preoptic area and to relate these to the expression of lordosis behavior. The first series of experiments test the hypothesis that E2 regulates alpha1- adrenoceptor gene expression, and more specifically, expression of the alpha1B subtype. This is a significant question because NE stimulation of alpha1-adrenoceptors facilitates estrous behavior and gonadotropin release in E2-primed female rats. Using molecular techniques (Northern blots, quantitative in situ hybridization) and receptor autoradiography, the time- and dose-dependent effects of E2 and alpha1 receptor mRNA and protein will be quantified in specific hypothalamic and preoptic area nuclei and correlated with the facilitation of lordosis behavior. We will also determine whether induction of alpha1 receptors occurs in neurons that express E2 receptors. The functional activity of alpha1 receptors will be monitored by assessing coupling of alpha1A and alpha1B receptor subtypes to both the cAMP and phosphoinositol second messenger systems as a function of steroid treatment. These studies should provide insight into the molecular mechanisms underlying the rapid, synergistic effects of P on lordosis responsiveness in E2-primed animals. The second series of experiments tests the hypothesis that E2 also acts by genomic mechanisms to desensitize beta-adrenoceptor function in the hypothalamus and preoptic area. This is an important question because a critical component of E2 facilitation of reproductive behavior may be the attenuation of inhibitory actions mediated by beta receptors. The time- and dose- dependent effects of E2 on beta receptor stimulation of cAMP formation will be correlated with the facilitation of lordosis behavior. In addition, the mechanism by which E2 desensitizes beta receptor-mediated signaling will be identified.